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Entinostat/恩替诺特 {[allProObj[0].p_purity_real_show]}

货号:A122285 同义名: 恩替诺特 (MS-275) / MS-275; SNDX-275

Entinostat是一种口服选择性I类HDAC抑制剂,对HDAC1、HDAC2和HDAC3的IC50值分别为243 nM、453 nM和248 nM。

Entinostat/恩替诺特 化学结构 CAS号:209783-80-2
Entinostat/恩替诺特 化学结构
CAS号:209783-80-2
Entinostat/恩替诺特 3D分子结构
CAS号:209783-80-2
Entinostat/恩替诺特 化学结构 CAS号:209783-80-2
Entinostat/恩替诺特 3D分子结构 CAS号:209783-80-2
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Entinostat/恩替诺特 纯度/质量文件 产品仅供科研

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产品名称 HD1 HD2 HDAC HDAC1 HDAC10 HDAC11 HDAC2 HDAC3 HDAC4 HDAC5 HDAC6 HDAC7 HDAC8 HDAC9 其他靶点 纯度
Givinostat HCl monohydrate ++++

HD1-B, IC50: 7.5 nM

HD1-A, IC50: 16 nM

+++

HD2, IC50: 10 nM

99%+
MC1568 ++

HD1-A (Maize), IC50: 100 nM

HD1-B (Maize), IC50: 3.4 μM

96%
Trichostatin A ++++

HDAC, IC50: ~1.8 nM

99%+
Scriptaid 99%+
Valproic acid sodium Autophagy 97%
AR-42 +++

HDAC, IC50: 30 nM

99%+
Dacinostat +++

HDAC, IC50: 32 nM

98+%
CUDC-101 ++++

HDAC, IC50: 4.4 nM

++++

HDAC1, IC50: 4.5 nM

+++

HDAC10, IC50: 26.1 nM

+++

HDAC2, IC50: 12.6 nM

++++

HDAC3, IC50: 9.1 nM

+++

HDAC4, IC50: 13.2 nM

+++

HDAC5, IC50: 11.4 nM

++++

HDAC6, IC50: 5.1 nM

+

HDAC7, IC50: 373 nM

++

HDAC8, IC50: 79.8 nM

++

HDAC9, IC50: 67.2 nM

EGFR,HER2 99%+
M344 ++

HDAC, IC50: 100 nM

99%+
Splitomicin +

Sir2p, IC50: 60 μM

99%
Panobinostat ++++

HDAC (MOLT-4 cells), IC50: 5 nM

HDAC (Reh cells), IC50: 20 nM

98%
Sodium 4-Phenylbutyrate 98%
Vorinostat +++

HDAC, IC50: ~10 nM

98%
Curcumin NF-κB,Nrf2 98%
Belinostat +++

HDAC, IC50: 27 nM

98%
RG-2833 ++

HDAC1, Ki: 32 nM

++

HDAC3, Ki: 5 nM

98%
Valproic acid +

HDAC1, IC50: 0.4 mM

98%
BG45 +

HDAC1, IC50: 2 μM

+

HDAC2, IC50: 2.2 μM

+

HDAC3, IC50: 289 nM

99%+
Entinostat +

HDAC1, IC50: 0.51 μM

+

HDAC3, IC50: 1.7 μM

98%
Resminostat +++

HDAC1, IC50: 42.5 nM

++

HDAC3, IC50: 50.1 nM

++

HDAC6, IC50: 71.8 nM

98+%
Romidepsin +++

HDAC1, IC50: 36 nM

+++

HDAC2, IC50: 47 nM

99%+
Parthenolide NF-κB,p53 97% HPLC
Tacedinaline +

HDAC1, IC50: 0.9 μM

+

HDAC2, IC50: 0.9 μM

+

HDAC3, IC50: 1.2 μM

98%
Mocetinostat ++

HDAC1, IC50: 0.15 μM

+

HDAC11, IC50: 0.59 μM

+

HDAC2, IC50: 0.29 μM

+

HDAC3, IC50: 1.66 μM

98%
WT-161 ++++

HDAC1, IC50: 8.35 nM

+++

HDAC2, IC50: 15.4 nM

++++

HDAC6, IC50: 0.4 nM

99%+
Fimepinostat ++++

HDAC1, IC50: 1.7 nM

++++

HDAC10, IC50: 2.8 nM

++++

HDAC11, IC50: 5.4 nM

++++

HDAC2, IC50: 5.0 nM

++++

HDAC3, IC50: 1.8 nM

+++

HDAC6, IC50: 27 nM

99%+
Tucidinostat ++

HDAC1, IC50: 95 nM

++

HDAC10, IC50: 78 nM

++

HDAC2, IC50: 160 nM

++

HDAC3, IC50: 67 nM

99%+
Santacruzamate A ++++

HDAC2, IC50: 119 pM

99%+
(E,E)-RGFP966 ++

HDAC3, IC50: 80 nM

99%+
LMK-235 +++

HDAC4, IC50: 11.9 nM

++++

HDAC5, IC50: 4.2 nM

99%+
Tasquinimod 99%+
CAY10603 ++++

HDAC6, IC50: 2 pM

98%
Tubastatin A +++

HDAC6, IC50: 15 nM

98%
Tubacin ++++

HDAC6, IC50: 4 nM

99%+
ACY-738 ++++

HDAC6, IC50: 1.7 nM

99%+
Nexturastat A ++++

HDAC6, IC50: 5 nM

99%+
BRD73954 +++

HDAC6, IC50: 36 nM

++

HDAC8, IC50: 120 nM

99%
Tubastatin A HCl +++

HDAC6, IC50: 15 nM

+

HDAC8, IC50: 854 nM

98%
PCI-34051 +++

HDAC8, IC50: 10 nM

99%+
Ricolinostat ++

HDAC1, IC50: 58 nM

++

HDAC2, IC50: 48 nM

++

HDAC3, IC50: 51 nM

++++

HDAC6, IC50: 4.7 nM

++

HDAC8, IC50: 100 nM

99%+
Droxinostat +

HDAC3, IC50: 16.9 μM

+

HDAC6, IC50: 2.47 μM

+

HDAC8, IC50: 1.46 μM

99%+
Abexinostat ++++

HDAC1, Ki: 7 nM

+++

HDAC10, IC50: 24 nM

+++

HDAC2, Ki: 19 nM

++++

HDAC3/SMRT, Ki: 8.2 nM

+++

HDAC6, Ki: 17 nM

+

HDAC8, IC50: 280 nM

98%+
Citarinostat +++

HDAC1, IC50: 35 nM

+++

HDAC2, IC50: 45 nM

+++

HDAC3, IC50: 46 nM

++++

HDAC6, IC50: 2.6 nM

++

HDAC8, IC50: 137 nM

99%+
HPOB +

HDAC1, IC50: 2.9 μM

+

HDAC10, IC50: 3.0 μM

+

HDAC2, IC50: 4.4 μM

+

HDAC3, IC50: 1.7 μM

++

HDAC6, IC50: 56 nM

+

HDAC8, IC50: 2.8 μM

97%
Quisinostat 2HCl ++++

HDAC1, IC50: 0.11 nM

++++

HDAC10, IC50: 0.46 nM

++++

HDAC11, IC50: 0.37 nM

++++

HDAC2, IC50: 0.33 nM

++++

HDAC3, IC50: 4.86 nM

++++

HDAC4, IC50: 0.64 nM

++++

HDAC5, IC50: 3.69 nM

++++

HDAC8, IC50: 4.26 nM

97%
Domatinostat +

HDAC1, IC50: 1.20 μM

+

HDAC10, IC50: 21 μM

+

HDAC11, IC50: 9.7 μM

+

HDAC2, IC50: 1.12 μM

+

HDAC3, IC50: 0.57 μM

+

HDAC5, IC50: 11.3 μM

+

HDAC9, IC50: 50 μM

99%+
TMP269 ++

HDAC4, IC50: 157 nM

++

HDAC5, IC50: 97 nM

+++

HDAC7, IC50: 43 nM

+++

HDAC9, IC50: 23 nM

99%+
Pracinostat ++

HDAC1, IC50: 49 nM

+++

HDAC10, IC50: 40 nM

++

HDAC11, IC50: 93 nM

++

HDAC2, IC50: 96 nM

+++

HDAC3, IC50: 43 nM

++

HDAC4, IC50: 56 nM

+++

HDAC5, IC50: 47 nM

+

HDAC6, IC50: 1.008 μM

++

HDAC7, IC50: 137 nM

++

HDAC8, IC50: 140 nM

++

HDAC9, IC50: 70 nM

99%+
TMP195 ++

HDAC4, Ki: 59 nM

++

HDAC5, Ki: 60 nM

+++

HDAC7, Ki: 26 nM

+++

HDAC9, Ki: 15 nM

99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

Entinostat/恩替诺特 生物活性

靶点
  • HDAC3

    HDAC3, IC50:1.7 μM

  • HDAC1

    HDAC1, IC50:0.51 μM

描述 The inhibition of class I HDACs increases the acetylation of histone proteins, which affects the tertiary chromatin structure and leads to altered expression of genes involved in cell proliferation, apoptosis and differentiation. Thus it makes a key role for inhibition of HDACs in anti-proliferation of tumor cells. Entinostat (MS-275) is a selective HDAC 1/2/3 inhibitor with IC50 values of 0.163, 0.396 and 0.605 μM, respectively[1]. A significant increased level of acetylated histone H3 can be observed in PBMCs treated with 5 nM entinostat for 24h. This hyperacetylation effect can also be observed in total cell extracts from PBMCs and tumor tissues in the mouse B16F10 melanoma models when treated orally with 50 mg/kg/day entinostat in a time-dependent manner. The anti-tumor efficacy of entinostat in vivo was proved in several experimental human tumor models with dose of 40 - 50 mg/kg/day, p.o., including MCF7, MDA-MB231, OVCAR3, HeLa-MaTu, DU145, H460, A549, LXF, HT29, HCT116, CAPAN1, 786-O and SK-Mel28 tumor bearing mice. A lot of gene-expression regulated through HDAC inhibition by entinostat are involved in this anti-tumor efficacy, including up-regulation of p21 in cell cycle, H2B in chromatin, CAECAM5 in cell communication and alpha-Tubulin in cytoskeleton, as well as down-regulation of TNFSF13 in apoptosis, HIF1-alpha in angiogenesis, and CTPS2 in metabolism[2]. Entinostat is in phase III for hormone receptor-positive advanced breast cancer and is in phase II for lung cancer, breast cancer, and Hodgkin lymphoma[3].
作用机制 The crystal structure of the HDAC2-benzamide complex reveals that the entinostat coordinates to the catalytic Zn2+ ion through both the carbonyl and amino groups to form an unusual 7-membered ring chelate complex[4].

Entinostat/恩替诺特 细胞实验

Cell Line
Concentration Treated Time Description References
MCF7 0.5μM, 5μM 1, 3, 6, 12, or 24 h significantly increased LIFR mRNA expression Oncogene. 2021 Aug;40(34):5314-5326.
MDA-MB-231b 0.5μM, 5μM 1, 3, 6, 12, or 24 h significantly increased LIFR mRNA expression Oncogene. 2021 Aug;40(34):5314-5326.
SKOV3 5 μM 12 h To investigate the effect of Entinostat combined with Niraparib on HRD-EXCUTE signature, results showed that the combination significantly enhanced the HRD-EXCUTE signature. Int J Biol Sci. 2023 Mar 21;19(6):1846-1860.
OVCAR5 5 μM 12 h To investigate the effect of Entinostat combined with Olaparib on HRD-EXCUTE signature, results showed that the combination significantly enhanced the HRD-EXCUTE signature. Int J Biol Sci. 2023 Mar 21;19(6):1846-1860.
Panc1 cells 500 nM 24 or 72 h To investigate the effect of Entinostat on pancreatic cancer cell differentiation, results showed that Entinostat significantly increased CD24 protein levels, indicating it promoted cell differentiation. Nucleic Acids Res. 2017 Jun 20;45(11):6334-6349.
BxPC3 cells 500 nM 24 or 72 h To investigate the effect of Entinostat on pancreatic cancer cell differentiation, results showed that Entinostat significantly increased CD24 protein levels, indicating it promoted cell differentiation. Nucleic Acids Res. 2017 Jun 20;45(11):6334-6349.
L3.6 cells 500 nM 24 or 72 h To investigate the effect of Entinostat on pancreatic cancer cell differentiation, results showed that Entinostat significantly increased CD24 protein levels, indicating it promoted cell differentiation. Nucleic Acids Res. 2017 Jun 20;45(11):6334-6349.
HMC3 microglia-like cells 10µM 24 h To assess the effect of Entinostat on DAM marker gene expression, results showed significant upregulation of SPP1 and CD9 expression bioRxiv [Preprint]. 2024 Oct 12:2024.10.11.617544.
HaCaT cells 10 μM 48 h To examine the effect of the HDAC inhibitor entinostat on DNA methylation, it was found that BG4 signal significantly increased in open chromatin promoter regions, and methylation levels at BG4 peaks were significantly reduced. Nat Struct Mol Biol. 2018 Oct;25(10):951-957.
human neuroendocrine SCLC cells 2.5 μM 24 h To investigate the effects of Entinostat on cell cycle and DNA damage in SCLC cells. Clin Cancer Res. 2023 Nov 14;29(22):4644-4659.
KU-OC-031065 0.25 μM 72 h Entinostat combined with olaparib significantly reduced the viability of KU-OC-031065 cells, showing synergistic effects. Gynecol Oncol. 2021 Jul;162(1):163-172.
KU-OC-033697 0.25 μM 72 h Entinostat combined with olaparib significantly reduced the viability of KU-OC-033697 cells, showing synergistic effects. Gynecol Oncol. 2021 Jul;162(1):163-172.
OVCAR-3 0.25 μM 72 h Entinostat combined with olaparib significantly reduced the viability of OVCAR-3 cells, showing synergistic effects. Gynecol Oncol. 2021 Jul;162(1):163-172.
SKOV-3 0.25 μM 72 h Entinostat combined with olaparib significantly reduced the viability of HR-proficient ovarian cancer cells, showing synergistic effects. Gynecol Oncol. 2021 Jul;162(1):163-172.
HNT34 1 μM 72 h To evaluate the antiproliferative effect of Entinostat on EVI1-high AML cells, results showed that Entinostat significantly inhibited cell proliferation. Nat Commun. 2024 Jun 4;15(1):4739.
UCSD/AML1 1 μM 72 h To evaluate the antiproliferative effect of Entinostat on EVI1-high AML cells, results showed that Entinostat significantly inhibited cell proliferation. Nat Commun. 2024 Jun 4;15(1):4739.
MOLM1 1 μM 72 h To evaluate the antiproliferative effect of Entinostat on EVI1-high AML cells, results showed that Entinostat significantly inhibited cell proliferation. Nat Commun. 2024 Jun 4;15(1):4739.
MEWO 1μM 72 h Entinostat combined with BRAF/MEK inhibitors significantly enhanced cell death, resulting in a 29% reduction in cell number. Cancer Discov. 2019 Apr;9(4):526-545.
SKMEL2 1μM 72 h Entinostat combined with BRAF/MEK inhibitors significantly enhanced cell death, resulting in a 29% reduction in cell number. Cancer Discov. 2019 Apr;9(4):526-545.
Hs695T 1μM 72 h Entinostat combined with BRAF/MEK inhibitors significantly enhanced cell death, resulting in a 29% reduction in cell number. Cancer Discov. 2019 Apr;9(4):526-545.
MCA205 cells 10 µM 6 h Entinostat treatment upregulated the mRNA expression of Cxcl9, 10, 11 Cancer Immunol Res. 2023 May 3;11(5):657-673.

Entinostat/恩替诺特 动物实验

Species
Animal Model
Administration Dosage Frequency Description References
Mice HRD ovarian cancer model Intraperitoneal injection 5 mg/kg Weekly for 4 weeks To investigate the effect of Entinostat combined with Niraparib on HRD ovarian cancer model, results showed that the combination significantly inhibited tumor growth and enhanced HRD-EXCUTE signature. Int J Biol Sci. 2023 Mar 21;19(6):1846-1860.
Mice MCF7 orthotopic inoculation model 10mg/kg 5 days/week until sacrifice Significantly reduced MCF7 primary tumor growth Oncogene. 2021 Aug;40(34):5314-5326.
SCID mice H841 xenograft model Entinostat: oral gavage, cisplatin: intraperitoneal injection 25 mg/kg Entinostat: twice a week, cisplatin: once a week, for 30 days Combination treatment with entinostat and cisplatin significantly decreased tumor growth in vivo. Tumor weights and intratumoral Pt content were significantly higher in the combination group, which also showed enhanced apoptosis and necrosis. Clin Cancer Res. 2023 Nov 14;29(22):4644-4659.
Mice SKOV-3-IP-Luc xenograft model Oral gavage 15 mg/kg Once weekly for two weeks Entinostat combined with olaparib significantly reduced peritoneal metastases in the SKOV-3 xenograft model and prolonged survival in the CCNE1-amplified HR-proficient PDX model. Gynecol Oncol. 2021 Jul;162(1):163-172.
Mice BRAF-mutant melanoma xenograft model Intraperitoneal injection 1mg/kg Once weekly for 2 weeks Entinostat combined with BRAF/MEK inhibitors significantly enhanced tumor regression, with an average 70% reduction in tumor volume. Cancer Discov. 2019 Apr;9(4):526-545.
Mice MC38 and MCA205 tumor models Oral 30 mg/kg Three times per week for 28 days Entinostat significantly suppressed the growth of MC38 and MCA205 tumors in immunocompetent mice but not in immunodeficient mice Cancer Immunol Res. 2023 May 3;11(5):657-673.

Entinostat/恩替诺特 动物研究

Dose Mice: min = 1 mg/kg[5] (i.p.), max = 49 mg/kg[6] (p.o.)
Administration i.p., p.o.
Pharmacokinetics
Animal Rats[7]
Dose 15 mg/kg
Administration p.o.
Cmax 8141.6 ± 2655.5 ng/ml
T1/2 9.8 ± 5.2 h
AUC0→∞ 13368.3 ± 3492.3 ng/ml·h
AUC0→t 13006.7 ± 3573.6 ng/ml·h
CL 1.2 ± 0.2 L/h/kg
Tmax 0.4 ± 0.2 h
MRT0→∞ 3.4 ± 1.4 h
Vd 16.9 ± 10.7 L/kg
MRT0→t 2.2 ± 0.3 h

Entinostat/恩替诺特 临床研究

NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03280563 Breast Neoplasms Phase 1 Phase 2 Recruiting October 7, 2022 -
NCT02623751 Breast Cancer Phase 1 Active, not recruiting February 2019 Japan ... 展开 >> Chikusa-ku, Aichi, Japan Chuo-ku, Osaka, Japan Chuo-ku, Tokyo, Japan 收起 <<
NCT00823290 Hepatocellular Carcinoma Phase 1 Unknown December 2010 Germany ... 展开 >> Department of Medicine 1, University Hospital Erlangen Recruiting Erlangen, Germany, 91054 Contact: Matthias Ocker, MD    +49-6421-58 ext 68931    Matthias.Ocker@staff.uni-marburg.de    Contact: Susanne Gahr, MD    +49-9131-85 ext 35000    susanne.gahr@uk-erlangen.de    Principal Investigator: Deike Strobel, MD 收起 <<

Entinostat/恩替诺特 参考文献

[1]Gao S, Zang J, et al. Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups. Bioorg Med Chem. 2017 Jun 15;25(12):2981-2994.

[2]Hess-Stumpp H, Bracker TU, et al. MS-275, a potent orally available inhibitor of histone deacetylases--the development of an anticancer agent. Int J Biochem Cell Biol. 2007;39(7-8):1388-405. Epub 2007 Feb 16.

[3]Yoon S, Eom GH, et al. HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016 Jan;52(1):1-11.

[4]Lombardi PM, Cole KE, et al. Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes. Curr Opin Struct Biol. 2011 Dec;21(6):735-43.

[5]Vendetti FP, Topper M, et al. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget. 2015 Jan 1;6(1):56-70.

[6]Saito A, Yamashita T, et al. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4592-7.

[7]Yang X, Zhang Q, et al. Pharmacokinetic interaction of entinostat and lapatinib following single and co-oral administration in rats. Xenobiotica. 2014 Nov;44(11):1009-13.

Entinostat/恩替诺特 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.28mL

2.66mL

1.33mL

26.57mL

5.31mL

2.66mL

Entinostat/恩替诺特 技术信息

CAS号209783-80-2
分子式C21H20N4O3
分子量 376.41
SMILES Code O=C(OCC1=CC=CN=C1)NCC2=CC=C(C(NC3=CC=CC=C3N)=O)C=C2
MDL No. MFCD08272435
别名 恩替诺特 (MS-275) ;MS-275; SNDX-275; MS 2275
运输蓝冰
InChI Key INVTYAOGFAGBOE-UHFFFAOYSA-N
Pubchem ID 4261
存储条件

In solvent -20°C:3-6个月-80°C:12个月

溶解方案

DMSO: 50 mg/mL(132.83 mM),配合低频超声,并水浴加热至45℃助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

请根据您的动物给药指南选择适当的溶解方案。
以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂:
——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
方案 一
方案 二
方案 三
方案 四
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